Many studies have been carried out to determine the effects of acid-base disturbances on the acid-base state of cardiac and skeletal muscle. In general these studies have been carried out under normoxic or hyperoxic conditions. However, in clinical situations in which the acid-base state is abnormal, there is frequently an accompanying degree of hypoxia. Therefore the objective of the proposed research is to assess to what extent hypoxia affects the cellular acid-base state and its regulation when various acid-base disturbances are imposed. Adult male rats will be placed in an environmental chamber in which the PO2, PCO2 and PN2 are regulated to produce varying degrees of hypoxia and hypercapnia. Animals exhibiting metabolic acidosis, produced by intraperitoneal injection of NH4C1, will be subjected to varying degrees of hypoxia and hypercapnia also. The duration of exposure to the various gas mixtures will range from 1 to 24 hours. At the end of the experimental period the animals will be anesthetized, a blood sample obtained, and skeletal and cardiac muscle removed for pCO2 pO2, lactate, pyruvate, 3H Inulin and 14C DMO. The tissue samples will be analyzed for 3H Inulin, 14C DMO, lactate, pyruvate, Cr, CrP and ATP. Intracellular pH of the tissue samples will be calculated from the distribution of 3H Inulin and 14C DMO. Analyses of the data will enable us to determine how hypoxia affects cellular acid-base regulation in vivo. In another series of experiments skeletal and cardiac muscle will be removed at the end of the experimental period. These tissues will be homogenized and the physico-chemical buffering of CO2 determined. The physiochemical buffering data will enable us to determine the contribution of changes in buffer composition to acid-base regulation in vivo. The results of this study will further our understanding of cellular acid-base regulation in conditions similar to those encountered clinically.